Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging

Gilead Sciences

Status and phase: Completed; Phase 4

Conditions: Myocardial Ischemia; Myocardial Perfusion Imaging

Treatments: Drug: Ranolazine; Drug: Placebo to match ranolazine; Behavioral: Exercise; Procedure: SPECT MPI

Study type: Interventional

Funder types: Industry

Identifiers

NCT01221272

GS-US-259-0103

Details and patient eligibility

About

This study enrolled participants with documented exercise-induced myocardial ischemia in order to evaluate whether ranolazine, when taken prior to exercise, can improve blood flow to the heart (myocardial perfusion), as assessed by exercise-induced myocardial perfusion defect size (PDS) and total perfusion deficit (TPD), using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

This was a 2-period crossover study. The last dose of each period must have been taken 3-4 hours prior to conduct of the exercise SPECT MPI. After the research exercise SPECT MPI was performed at the end of Period 1, participants discontinued the treatment they were randomized to for that period and began the other treatment in Period 2.

Enrollment: 81 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Exercise SPECT MPI study (stress and rest) showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear laboratory using Corridor4DM imaging software) performed not more than 12 weeks prior to screening, OR
• Exercise SPECT MPI study (stress and rest) conducted during screening (after consultation with the Medical Monitor and after informed consent was obtained) showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear laboratory)
• Stable antianginal medical therapy (excluding short-acting nitroglycerin)

Key Exclusion Criteria:

• Left bundle branch block
• Automated implantable defibrillator and/or pacemaker (selected subjects with permanent pacemakers who had an intact sinus mechanism may have been included following consultation with the Medical Monitor)
• Intervening coronary revascularization between the time of qualifying exercise SPECT MPI study and randomization
• Acute myocardial infarction (MI) within 60 days prior to screening or at any time after the qualifying exercise SPECT MPI study, or MI undergoing staged intervention during a subject's participation in the trial
• Unstable angina within 30 days prior to screening, or at any time after the qualifying exercise SPECT MPI study
• Coronary artery bypass graft surgery within 60 days prior to screening or at any time after the qualifying exercise SPECT MPI study, or percutaneous coronary intervention within 30 days prior to screening or at any time after the qualifying exercise SPECT MPI study
• Anticipated coronary revascularization during the trial period
• Cerebrovascular attack or transient ischemic attack within 90 days prior to screening
• History of serious arrhythmias
• Current atrial fibrillation or atrial flutter
• QTc interval > 500 milliseconds
• Diagnosed as having New York Heart Association Class III or IV heart failure
• Inability to exercise or exercise limitation due to other comorbidities that may have interfered with ability to perform required exercise SPECT MPI study
• Body mass index greater than or equal to 38 kg/m^2 (may have been up to 40 kg/m^2 after consultation with the Medical Monitor)
• Any absolute contraindications to exercise stress testing

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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81 participants in 2 patient groups

Ranolazine/Placebo

Experimental group

Description:

Participants received ranolazine from Day 1 through Day 15 (± 2 days) of Period 1, followed by an exercise SPECT MPI study, then received placebo to match ranolazine from Day 1 through Day 15 (± 2 days) of Period 2, followed by an exercise SPECT MPI study.

Treatment:

Behavioral: Exercise

Drug: Placebo to match ranolazine

Procedure: SPECT MPI

Drug: Ranolazine

Placebo/Ranolazine

Experimental group

Description:

Participants received placebo to match ranolazine from Day 1 through Day 15 (± 2 days) of Period 1, followed by an exercise SPECT MPI study, then received ranolazine from Day 1 through Day 15 (± 2 days) of Period 2, followed by an exercise SPECT MPI study.

Treatment:

Behavioral: Exercise

Drug: Placebo to match ranolazine

Procedure: SPECT MPI

Drug: Ranolazine